Resolving the neural circuits of anxiety

A mechanistic understanding of anxiety is required to advance the development of next-generation therapies for anxiety disorders. In this Review, Calhoon and Tye discuss recent insights into the circuit physiology driving anxiety-like behavior gained through the application of modern approaches in neuroscience. Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.